Bone-Targeted Therapies for Men With Prostate Cancer Receiving Androgen-Deprivation Therapy

Key Points

Oral and intravenous bisphosphonates and denosumab improve bone mineral density in men with nonmetastatic prostate cancer who are receiving androgen-deprivation therapy. However, it is unclear whether bisphosphonates reduced bone fractures.

Denosumab was also effective in reducing the risk for radiographic vertebral fractures, based on the results of one trial.

Among men diagnosed with prostate cancer, about one in two will receive androgen-deprivation therapy, which is associated with many potential adverse side effects, including significant bone loss and increased risk for low trauma or fragility fractures similar to those found in people with primary osteoporosis. A study by Alibhai et al investigating the effectiveness of drug, supplement, and lifestyle interventions aimed at preventing fracture, improving bone mineral density, or preventing or delaying osteoporosis in men with nonmetastatic prostate cancer receiving androgen-deprivation therapy has found that both bisphosphonates and denosumab (Prolia, Xgeva) improve bone mineral density in these patients. However, although evidence showed bisphosphonates improved bone mineral density, it is unclear whether they reduced bone fractures. The study was published in the Annals of Internal Medicine.

Study Methodology

The researchers reviewed literature searches on the results of randomized controlled trials of men with nonmetastatic prostate cancer and the intervention involved therapies, including drug, supplement, or lifestyle modification, directed at improving bone health, bone mineral density, and delaying or avoiding the development of osteoporosis. The searches were performed in Ovid MEDLINE (1946 to January 2017), EMBASE (1980 to January 2017), and the Cochrane Database of Systematic Reviews (January 2017).

Study Results

Two systematic reviews and 28 reports of 27 trials met inclusion criteria. All the trials focused on men with nonmetastatic prostate cancer who were initiating or continuing androgen-deprivation therapy. Bisphosphonates were effective in increasing bone mineral density, but no trial was sufficiently powered to detect reduction in fractures. Denosumab improved bone mineral density and reduced the incidence of new radiographic vertebral fractures in one high-quality trial. No trials compared calcium or vitamin D vs placebo. Three lifestyle intervention trials did not show a statistically significant difference in change in bone mineral density between exercise and usual care.

“Men with nonmetastatic prostate cancer who are receiving [androgen-deprivation therapy] are at risk for loss of [bone mineral density] and fractures. Robust evidence showing fracture reduction is restricted to one approved drug (denosumab). Evidence from [randomized clinical trials] supporting improvements in [bone mineral density] has been found for oral and intravenous bisphosphonates, but whether this is associated with reduced fractures remains unclear. Further trials powered to detect reduction in clinical fractures are needed,” concluded the study researchers.

Funding for this study was provided by the Program in Evidence-Based Care. The corresponding author for this study is Shabbir M.H. Alibhai, MD, MSc, of the University of Toronto.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.